CN101671286B - Method for preparing benzoyl-1,3-cyclohexanedione compound - Google Patents
Method for preparing benzoyl-1,3-cyclohexanedione compound Download PDFInfo
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Abstract
The invention provides a method for preparing benzoyl-1,3-cyclohexanedione compound, and the benzoyl-1,3-cyclohexanedione compound is shown by the structural formula (I), wherein R1 is nitryl, chlorine, bromine or iodine, R2, R3, R4 and R5 are the same as or different from each other and respectively and independently selected from H or the alkyl of C1-C4, and R6 is H, halogen, the alkyl of C1-C4, the alkoxy of C1-C4, cyano or nitryl; and the method leads the compound shown in the structural formula (II) to be hydrolyzed under the alkaline condition and then have decarboxylation reaction under the acidic condition, wherein R7 is the alkyl of C1-C4. By adopting the method for preparing the benzoyl-1,3-cyclohexanedione compound, higher yield can be obtained; and furthermore, the benzoyl-1,3-cyclohexanedione compound in the prepared product has high purity.
Description
Technical field
The present invention relates to the preparation method of a kind of benzoyl-hydroresorcinol compounds.
Background technology
Benzoyl shown in structural formula (I)-hydroresorcinol compounds,
Structural formula (I):
Wherein, R
1Be nitro, chlorine, bromine or iodine, R
2-R
5Be hydrogen or C
1-C
4Alkyl, R
6Be hydrogen, halogen, C
1-C
4Alkyl, C
1-C
4Alkoxyl group, cyano group or nitro.Described benzoyl-hydroresorcinol compounds has weeding activity, for example, works as R
1Be chlorine, R
2-R
6During for hydrogen, described benzoyl-hydroresorcinol compounds is a weedicide sulphur humulone (sulcotrione); Work as R
1Be nitro, R
2-R
6During for hydrogen, benzoyl-hydroresorcinol compounds is weedicide mesotrione (mesotrione).Sulphur humulone and mesotrione have special mechanism of action, are the inhibitor of the two oxydase (HPPD) of p-hydroxybenzene pyruvic acid, can be used as corn field herbicide, broad weed-killing spectrum, prevention effect is good, to crop, environment and succession crop safety, uses very extensive.
CN 85109771A discloses the preparation method of the 2-shown in the following structural formula (2 '-nitro benzoyl)-hydroresorcinol compounds,
Yet, adopt the yield of method for preparing weedicide mesotrione very low, yield only is 30-40% usually.
Summary of the invention
The present invention is in order to overcome existing 2-(2 '-nitro benzoyl)-1; the shortcoming that the preparation method's of hydroresorcinol compounds yield is very low; a kind of new preparation benzoyl-1 is provided; the method of hydroresorcinol compounds; adopt the yield of benzoyl-hydroresorcinol compounds that this method makes very high.
The present inventor is surprised to find that; by on 4 of cyclohexanedione ring, introducing big electron-withdrawing group (alkoxymethyl)-2 acyl group; make that the ketone group steric hindrance on 3 is bigger; be not easy to react with carboxylic acid halides; thereby improved the selectivity of 1 ketone group and carboxylic acid halides reaction greatly; and the sucting electronic effect of (alkoxymethyl)-2 acyl group makes the hydrogen on 2 more active; help the carrying out that ketenes is converted into the translocation reaction of diketone; and the (alkoxymethyl)-2 acyl group can be sloughed by simple hydrolysis and decarboxylic reaction after translocation reaction is finished; because hydrolysis and decarboxylic reaction carry out easily and can fully carry out; therefore; although compared hydrolysis many and the step of decarboxylic reaction with above-mentioned CN 85109771A disclosed method; but the yield of benzoyl-hydroresorcinol compounds does not only reduce, and has improved greatly on the contrary.
The invention provides the preparation method of a kind of benzoyl-hydroresorcinol compounds, described benzoyl-hydroresorcinol compounds shown in structural formula (I),
Wherein, R
7Be C
1-C
4Alkyl.
Adopt preparation benzoyl-1 provided by the invention; the method of hydroresorcinol compounds can obtain very high yield; for example up to more than 70%; and; benzoyl in the prepared product-1; the purity of hydroresorcinol compounds is very high, and for example GC purity is up to more than 98%, and by product is few.
Embodiment
The invention provides the preparation method of a kind of benzoyl-hydroresorcinol compounds, described benzoyl-hydroresorcinol compounds shown in structural formula (I),
Wherein, R
7Be C
1-C
4Alkyl, be preferably methyl or ethyl.
In described method provided by the invention, the pH value of described alkaline condition can be 8-12, is preferably 9-11; The pH value of described acidic conditions can be 1-6, is preferably 3-4.Reaction times in described alkaline condition can be 0.5-5 hour, and the reaction times in described acidic conditions can be 1-3 hour.The pH value of described alkaline condition can be regulated with the alkali of various routines, for example can be with at least a adjusting the in lithium hydroxide, sodium hydroxide and the potassium hydroxide; The pH value of described acidic conditions can be regulated for the acid with various routines, for example can be with at least a adjusting the in hydrochloric acid, sulfuric acid, the phosphoric acid.
In a kind of preferred implementation of the present invention, the compound of described structural formula (II) can make by making the compound shown in the structural formula (III) carry out translocation reaction in the presence of catalyzer and organic solvent,
Above-mentioned preferred embodiment in, described catalyzer can be for promoting the various catalyzer of translocation reaction, for example can be the 4-Dimethylamino pyridine, acetone cyanohydrin, sodium cyanide, potassium cyanide, cuprous cyanide, at least a in zinc chloride and the aluminum chloride, in order to obtain better catalyst effect, thereby improve the yield of the finished product, described catalyzer is preferably 4-Dimethylamino pyridine and/or acetone cyanohydrin, most preferably be the mixture of 4-Dimethylamino pyridine and acetone cyanohydrin, and in described mixture, the mol ratio of 4-Dimethylamino pyridine and acetone cyanohydrin is 0.5-2: 1.When described catalyzer is the mixture of 4-Dimethylamino pyridine and acetone cyanohydrin, and in the time of in the scope of above-mentioned blending ratio, described mixture can play significant promoter action to described translocation reaction, the conversion of compounds rate that makes the compound of structural formula (III) be converted into structural formula (II) is more than 95%, thereby the yield that makes final product is up to more than 85%.The mol ratio that described catalyst consumption is preferably with the compound of described structural formula (III) is 0.02-0.5: 1, and 0.05-0.2 more preferably: 1,0.05-0.1 more preferably: 1.
The organic solvent that uses in the described translocation reaction can be as in benzene,toluene,xylene, ethylene dichloride, tetracol phenixin, trichloromethane and the methylene dichloride at least a, be preferably toluene and/or trichloromethane.There is no particular limitation for the consumption of described organic solvent, as long as described reactant and catalyzer can fully be dissolved, under the preferable case, the mol ratio of the compound of the consumption of described organic solvent and described structural formula (III) is 10-25: 1.
Can monitor the degree that described translocation reaction carries out by high performance liquid chromatography-mass spectrometry (HPLC-MS), when the conversion of compounds rate that is converted into described structural formula (II) when the compound of described structural formula (III) no longer increases, can judge that described translocation reaction finishes.The time that the compound of described structural formula (III) participates in reaction was generally 3-5 hour, was preferably 3.5-4.5 hour, and described reaction can preferably be carried out under 15-55 ℃ under 0-110 ℃.In addition, can be the compound of described structural formula (II) by the compound reaction back products therefrom that nmr spectrum data characterizes described structural formula (III).
In above-mentioned preferred implementation, the compound of described reaction resulting structures formula (II) can separate or directly be hydrolyzed and decarboxylic reaction without separating purification.
In the embodiment of present invention further optimization, the compound of described structural formula (III) can be carried out condensation reaction and made by compound shown in the structural formula (IV) and the compound shown in the structure formula V in the presence of acid binding agent and organic solvent,
Wherein, X is a halogen, is preferably chlorine.
In the structural formula of the compound of described structural formula (IV), on 1 and 3 of cyclohexanedione ring, the (alkoxymethyl)-2 acyl group is on 4 of cyclohexanedione ring, and the carbon potential on the described cyclohexanedione ring is numbered in the direction of the clock respectively for two ketone groups.
In the structural formula of the compound of described structure formula V, acid halide group is at 1 of phenyl ring, R
1On 2 of phenyl ring, methylsulfonyl is on 4 of phenyl ring, and the carbon potential on the described phenyl ring is numbered in the direction of the clock.
In the compound of described structural formula (IV); 4 steric hindrances that go up the (alkoxymethyl)-2 acyl group are bigger; therefore; the existence of (alkoxymethyl)-2 acyl group; make that the ketone group steric hindrance on 3 is bigger; be not easy to react, generate the selectivity of the compound of described structural formula (III) thereby improved greatly, and then can effectively prevent production of by-products in the reaction system by the compound of described structural formula (IV) and the compound reaction of described structure formula V with described structure formula V.
In above-mentioned further preferred embodiment, the mol ratio of the compound of the compound of described structure formula V and described structural formula (IV) can be 0.9-1.2: 1, be preferably 1-1.1: and 1,1-1.01 more preferably: 1.
Described acid binding agent can for various can with acid-respons or bonded material, for example can be in various organic amines, pyridine, the alkaline carbonate at least a, described organic amine for example can be at least a in ammoniacal liquor, methylamine, ethamine, dimethylamine, diethylamine, dipropyl amine, quadrol, Trimethylamine 99, triethylamine, the tripropyl amine, and described alkaline carbonate for example can be yellow soda ash and/or salt of wormwood.The preferred described acid binding agent of the present invention is at least a in Trimethylamine 99, triethylamine, tripropyl amine, pyridine, yellow soda ash and the salt of wormwood, and further under the preferable case, described acid binding agent is a triethylamine.There is no particular limitation for the consumption of described acid binding agent, can add described acid binding agent with the consumption of routine, and under the preferable case, the mol ratio of the compound of the consumption of described acid binding agent and described structural formula (IV) is 1-5: 1, and 1-2 more preferably: 1.The organic solvent that uses in the reaction of the compound of described structural formula (IV) and the compound of described structure formula V can be as in benzene,toluene,xylene, ethylene dichloride, tetracol phenixin, trichloromethane and the methylene dichloride at least a, be preferably toluene and/or trichloromethane.There is no particular limitation for the consumption of described organic solvent, as long as described reactant and acid binding agent can fully be dissolved, under the preferable case, the mol ratio of the compound of the consumption of described organic solvent and described structural formula (IV) is 10-25: 1.
Condensation reaction between the ketone group on 1 of the compound of acyl halide group on the compound of described structure formula V and described structural formula (IV) can be under 0-110 ℃, preferably under 10-60 ℃, carry out, reaction times was generally 0.5-2 hour, was preferably 1-1.5 hour.
Can monitor the degree that the condensation reaction between described acyl halide group and the described ketone group is carried out by gas chromatography-mass spectrometry (GC-MS), when the conversion of compounds rate of described structural formula (IV) no longer increases, can judge that described reaction finishes.In addition, can be the compound shown in the formula (III) by the compound reaction products therefrom that nmr spectrum data characterizes the compound of described structural formula (IV) and described structure formula V.
In above-mentioned further preferred embodiment, the compound of described reaction resulting structures formula (III) can separate or without separate to purify and directly carry out translocation reaction.
In above-mentioned further preferred embodiment, the concrete reaction process of described preparation benzoyl-hydroresorcinol compounds is as follows:
In most preferred embodiment of the present invention, the compound of described structural formula (IV) is preferably R in the structural formula (IV)
2-R
5Be hydrogen, R
7Be the compound of methyl or ethyl, as described R
7During for methyl, the compound of described structural formula (IV) is 4-methoxy methyl acyl group-hydroresorcinol; As described R
7During for ethyl, the compound of described structural formula (IV) is 4-ethoxy acetyl-hydroresorcinol.4-methoxy methyl acyl group-1, hydroresorcinol and 4-ethoxy acetyl-1, hydroresorcinol all can be according to well known to a person skilled in the art that method and condition prepare, for example, described 4-methoxy methyl acyl group-hydroresorcinol can make by making dimethyl malonate and 3-butene-2-ketone carry out contact reacts; Described 4-ethoxy acetyl-hydroresorcinol can make diethyl malonate and 3-butene-2-ketone carry out contact reacts and make.Described 4-methoxy methyl acyl group-1; hydroresorcinol and 4-ethoxy acetyl-1; reaction conditions in the preparation process of hydroresorcinol can be for carrying out back flow reaction in lower alcohol such as methyl alcohol, ethanolic soln; reaction times is 4-10 hour, and the mol ratio of described ester and described ketone is 1-1.5: 1.
The compound of described structure formula V is preferably R in the structure formula V
1Be nitro or chlorine, R
6For hydrogen, X are the compound of chlorine, the compound of promptly described structure formula V is 2-nitro-4-methylsulfonyl Benzoyl chloride or 2-chloro-4-methylsulfonyl Benzoyl chloride.When the compound of the compound of described structural formula (IV) and structure formula V meets above-mentioned preferable case; described method provided by the invention is mainly used in preparation sulphur humulone (2-(2-chloro-4-methylsulfonyl) phenyl acyl group-1; hydroresorcinol) or mesotrione (2-(2-nitro-4-methylsulfonyl) phenyl acyl group-hydroresorcinol).
The present invention is further detailed explanation by the following examples.
Preparation example 1
The preparation of 4-methoxy methyl acyl group-hydroresorcinol
(0.1 mole of the methanol solution that in 250 milliliters reaction flask, adds the sodium methylates of 11.9 grams successively, concentration is 27 weight %), (0.11 mole of the dimethyl malonate of 14.7 grams, 99 weight %), under agitation drip and contain (0.1 mole of the 7.3 3-butene-2-ketone that restrain, 96 weight %) methanol solution (20 milliliters of anhydrous methanols), the speed of dropping is 1 droplet/second; Carried out back flow reaction after dropwising 6 hours, the GC-MS analysis is carried out in sampling, and the transformation efficiency of learning 3-butene-2-ketone is 99.5%.Then, methyl alcohol is reclaimed in underpressure distillation, and makes resistates be cooled to 25 ℃; adding 100 milliliters of entry, is the hydrochloric acid soln adjusting pH value to 4 of 30 weight % with concentration afterwards, uses ethyl acetate extraction again 3 times; remove solvent, thereby make the 4-methoxy methyl acyl group-hydroresorcinol of 15.1 grams.Sampling is carried out the GC-MS analysis and is learnt that purity is 95.2%, and yield is 84.6%.The nmr spectrum data of products therefrom as:
1HNMR (500MHz, CDCl
3): δ 2.04 (m, 1H), 2.35-2.47 (m, 3H), 3.18 (m, 1H), 3.56-3.67 (m, 5H).
Preparation example 2
The preparation of 4-ethoxy acetyl-hydroresorcinol
In 250 milliliters reaction flask, add (0.1 mole of 37.8 alcohol sodium alcohol solution that restrain successively, concentration is 18 weight %), (0.12 mole of the diethyl malonate of 19.4 grams, 99 weight %), under agitation drip and contain (0.1 mole of the 7.3 3-butene-2-ketone that restrain, 96 weight %) ethanolic soln (20 milliliters of dehydrated alcohols), the speed of dropping is 1 droplet/second; Carried out back flow reaction after dropwising 5.5 hours, the GC-MS analysis is carried out in sampling, and the transformation efficiency of learning 3-butene-2-ketone is 99.2%.Then; ethanol is reclaimed in underpressure distillation; and make resistates be cooled to 25 ℃; adding 100 milliliters of entry, is the hydrochloric acid soln adjusting pH value to 4 of 30 weight % with concentration afterwards, uses ethyl acetate extraction again 3 times; merge organic phase; remove solvent, thereby make the 4-ethoxy acetyl-hydroresorcinol of 16.5 grams.Sampling is carried out the GC-MS analysis and is learnt that purity is 96.8%, and yield is 86.8%.The nmr spectrum data of products therefrom is as follows:
1H NMR (500MHz, CDCl
3): δ 1.27 (m, 3H), 2.33-2.51 (m, 3H), 3.16 (m, 1H), 3.58-3.64 (m, 3H), 4.25 (m, 2H).
Preparation example 3
4-methoxy methyl acyl group-6-methyl isophthalic acid, the preparation of hydroresorcinol
(0.1 mole of the methanol solution that in 250 milliliters reaction flask, adds the sodium methylates of 11.9 grams successively, concentration is 27 weight %), (0.11 mole of the dimethyl malonate of 14.7 grams, 99 weight %), under agitation drip (0.1 mole of the 3-methyl contain 8.8 grams-3-butene-2-ketone, 96 weight %) methanol solution (20 milliliters of anhydrous methanols), the speed of dropping is 1 droplet/second; Carried out back flow reaction after dropwising 6 hours, the GC-MS analysis is carried out in sampling, and the transformation efficiency of learning 3-methyl-3-butene-2-ketone is 99.1%.Then; methyl alcohol is reclaimed in underpressure distillation; and make resistates be cooled to 25 ℃; add 100 milliliters of entry; be the hydrochloric acid soln adjusting pH value to 4 of 30 weight % with concentration afterwards, use ethyl acetate extraction again 3 times, remove solvent; thereby make the 4-methoxy methyl acyl group-6-methyl isophthalic acid of 16.4 grams, hydroresorcinol.Sampling is carried out the GC-MS analysis and is learnt that purity is 96.1%, and yield is 85.7%.The nmr spectrum data of products therefrom as:
1H NMR (500MHz, CDCl
3): δ 1.11 (m, 3H), 2.02 (m, 1H), 2.28 (m, 1H), 2.51 (m, 1H), 3.19 (m, 1H), 3.57-3.67 (m, 5H).
Embodiment 1
Present embodiment is used to illustrate the preparation method of benzoyl provided by the invention-hydroresorcinol compounds.
(1) under nitrogen protection; the 4-methoxy methyl acyl group-1 that in 500 milliliters reaction flask, adds preparation in 0.1 mole the preparation example 1 successively; the toluene (1.4 moles) of hydroresorcinol and 150 milliliters; under agitation drip 0.1 mole triethylamine; then in 15 ℃ water-bath environment; dropping contains the toluene solution (50 milliliters of toluene) of 2-nitro-4-methylsulfonyl Benzoyl chloride of 0.1 mole, after dropwising, continues down to stir 1 hour at 25 ℃.Sampling is carried out the GC-MS analysis and is learnt that the transformation efficiency of 4-methoxy methyl acyl group-hydroresorcinol is 98.2%.The water that adds 100 milliliters then stirred 30 minutes, left standstill, and removed water layer, used 50 milliliters water washing organic layer again, after solvent toluene is sloughed in the organic layer decompression, made the compound shown in 0.095 mole the following structural formula,
(2) under 25 ℃, the described compound of preparation in (1) is added in 150 milliliters the toluene (1.4 moles), then to wherein adding 0.005 mole 4-Dimethylamino pyridine and 0.005 mole acetone cyanohydrin, behind the stirring reaction 3 hours, sampling is carried out the HPLC-MS analysis and is learnt that the described conversion of compounds rate that makes in (1) is 98.5%.Then, add 200 ml waters, stir after 20 minutes, leave standstill, remove water layer, use 50 milliliters water washing organic layer again, described organic layer makes the compound shown in 0.091 mole the following structural formula after solvent toluene is sloughed in decompression,
The nmr spectrum data of described compound is as follows:
1HNMR (500MHz, CDCl
3): δ 1.67 (m, 1H), 1.92-2.01 (m, 3H), 3.19 (m, 1H), 3.25 (s, 3H), 3.69 (s, 3H), 7.62 (m, 1H), 8.46 (m, 1H), 8.85 (m, 1H), 16.53 (s, 1H).
(3) compound dissolution that makes preparation in (2) is in 120 milliliters water, and be that the sodium hydroxide solution of 1 mol is regulated pH value to 10 with concentration, stir and be heated to backflow, back flow reaction 4 hours is carried out the HPLC-MS analysis by sampling and is learnt that the conversion of compounds rate that makes in (2) is 98.6%.Then; be cooled to 25 ℃; and with 100 milliliters ethyl acetate extraction 2 times; water layer concentration is the salt acid for adjusting pH value to 4 of 30 weight %, reheat to 50 ℃, insulation reaction 2 hours; be cooled to 25 ℃ afterwards; and, merge organic layer, and use anhydrous magnesium sulfate drying with 150 milliliters ethyl acetate extraction 2 times; filter; remove solvent, use the methanol aqueous solution recrystallization again, the light yellow solid that obtains 26.6 grams (contains 0.085 mole 2-(2-nitro-4-methylsulfonyl) phenyl acyl group-1; hydroresorcinol; be also referred to as mesotrione), purity is 98.4%, yield is 85%.
Embodiment 2
Present embodiment is used to illustrate the preparation method of benzoyl provided by the invention-hydroresorcinol compounds.
(1) under nitrogen protection; the 4-ethoxy acetyl-1 that in 1 liter reaction flask, adds preparation in 0.1 mole the preparation example 2 successively; the trichloromethane (1.85 moles) of hydroresorcinol and 150 milliliters; under agitation drip 0.3 mole Trimethylamine 99; then in 25 ℃ water-bath environment; dropping contains the chloroform soln (50 milliliters of trichloromethanes) of 0.11 mole 2-chloro-4-methylsulfonyl Benzoyl chloride, after dropwising, continues down to stir 2 hours at 25 ℃.It is 98.8% that the transformation efficiency of learning 4-ethoxy acetyl-hydroresorcinol is analyzed in sampling.The water that adds 100 milliliters then stirred 30 minutes, left standstill, and removed water layer, used 50 milliliters water washing organic layer again, after solvent toluene is sloughed in the organic layer decompression, made the compound shown in 0.096 mole the following structural formula,
(2) under 55 ℃, the described compound of preparation in (1) is added in 150 milliliters the trichloromethane (1.85 moles), then to the acetone cyanohydrin that wherein adds 0.002 mole, behind the stirring reaction 3 hours, sampling is carried out the HPLC-MS analysis and is learnt that the described conversion of compounds rate that makes in (1) is 94.9%.Then, add 200 ml waters, stir after 20 minutes, leave standstill, remove water layer, use 50 milliliters water washing organic layer again, described organic layer makes the compound shown in 0.089 mole the following structural formula after solvent toluene is sloughed in decompression,
(3) compound dissolution that makes preparation in (2) is in 120 milliliters water, and be that the sodium hydroxide solution of 1 mol is regulated pH value to 11 with concentration, stir and be heated to backflow, back flow reaction is 3 hours then, carries out the HPLC-MS analysis by sampling and learns that the conversion of compounds rate that makes in (2) is 99.1%.Then; be cooled to 25 ℃; and with 100 milliliters ethyl acetate extraction 2 times; water layer concentration is the salt acid for adjusting pH value to 3 of 30 weight %, reheat to 50 ℃, insulation reaction 2.5 hours; be cooled to 25 ℃ afterwards; and, merge organic layer, and use anhydrous magnesium sulfate drying with 150 milliliters ethyl acetate extraction 2 times; filter; remove solvent, use the methanol aqueous solution recrystallization again, the white solid that obtains 24.47 grams (contains 0.081 mole 2-(2-chloro-4-methylsulfonyl) phenyl acyl group-1; hydroresorcinol; be also referred to as the sulphur humulone), purity is 98.8%, yield is 81%.
Embodiment 3
Present embodiment is used to illustrate the preparation method of benzoyl provided by the invention-hydroresorcinol compounds.
(1) under nitrogen protection; the 4-methoxy methyl acyl group-6-methyl isophthalic acid that in 500 milliliters reaction flask, adds preparation in 0.1 mole the preparation example 3 successively; the toluene (1.4 moles) of hydroresorcinol and 150 milliliters; under agitation drip 0.1 mole triethylamine; then in 15 ℃ water-bath environment; dropping contains the toluene solution (50 milliliters of toluene) of 2-nitro-4-methylsulfonyl Benzoyl chloride of 0.1 mole, after dropwising, continues down to stir 1 hour at 25 ℃.Sampling is carried out the GC-MS analysis and is learnt 4-methoxy methyl acyl group-6-methyl isophthalic acid, and the transformation efficiency of hydroresorcinol is 98.5%.The water that adds 100 milliliters then stirred 30 minutes, left standstill, and removed water layer, used 50 milliliters water washing organic layer again, after solvent toluene is sloughed in the organic layer decompression, made the compound shown in 0.091 mole the following structural formula,
(2) under 25 ℃, the described compound of preparation in (1) is added in 150 milliliters the toluene (1.4 moles), then to wherein adding 0.005 mole 4-Dimethylamino pyridine and 0.005 mole acetone cyanohydrin, behind the stirring reaction 3 hours, sampling is carried out the HPLC-MS analysis and is learnt that the described conversion of compounds rate that makes in (1) is 98.3%.Then, add 200 ml waters, stir after 20 minutes, leave standstill, remove water layer, use 50 milliliters water washing organic layer again, described organic layer makes the compound shown in 0.09 mole the following structural formula after solvent toluene is sloughed in decompression,
(3) compound dissolution that makes preparation in (2) is in 120 milliliters water, and be that the sodium hydroxide solution of 1 mol is regulated pH value to 9 with concentration, stir and be heated to backflow, back flow reaction 4 hours is carried out the HPLC-MS analysis by sampling and is learnt that the conversion of compounds rate that makes in (2) is 98.6%.Then; be cooled to 25 ℃; and with 100 milliliters ethyl acetate extraction 2 times; water layer concentration is the salt acid for adjusting pH value to 5 of 30 weight %; reheat to 50 ℃, insulation reaction 2 hours is cooled to 25 ℃ afterwards; and with 150 milliliters ethyl acetate extraction 2 times; merge organic layer, and use anhydrous magnesium sulfate drying, filter; remove solvent; use the methanol aqueous solution recrystallization again, obtain the faint yellow solid (containing 0.082 mole 2-(2-nitro-4-methylsulfonyl) phenyl acyl group-6-methyl isophthalic acid, hydroresorcinol) of 36.9 grams; purity is 98.1%, and yield is 83.5%.
Embodiment 4
Present embodiment is used to illustrate the preparation method of benzoyl provided by the invention-hydroresorcinol compounds.
Method according to embodiment 1 prepares mesotrione (2-(2-nitro-4-methylsulfonyl) phenyl acyl group-1; hydroresorcinol); different is that catalyzer used in the step (2) is 0.01 mole a sodium cyanide; thereby the light yellow solid that finally makes 22.25 grams (contains 0.071 mole 2-(2-nitro-4-methylsulfonyl) phenyl acyl group-1; hydroresorcinol; be also referred to as mesotrione), purity is 98.3%, yield is 71%.
This shows; though in described method provided by the invention; on 4, has 1 of methoxy methyl acyl group; hydroresorcinol analog derivative and the reaction of 4-methylsulfonyl benzoyl derivatives are with preparation benzoyl-1; the preparation method of hydroresorcinol compounds has had more the step of hydrolysis and decarboxylation than existing method; but yield of the present invention still can be up to more than 70%, far above the yield of 30-40% of the prior art.
Claims (10)
1. the preparation method of benzoyl-hydroresorcinol compounds, described benzoyl-hydroresorcinol compounds shown in structural formula (I),
Wherein, R
1Be nitro, chlorine, bromine or iodine, R
2-R
5Identical or different, be selected from hydrogen or C independently of one another
1-C
4Alkyl, R
6Be hydrogen, halogen, C
1-C
4Alkyl, C
1-C
4Alkoxyl group, cyano group or nitro, it is characterized in that described method comprises is hydrolyzed the compound shown in the structural formula (II) under alkaline condition, carry out decarboxylic reaction then under acidic conditions,
Wherein, R
1-R
6Definition identical with formula (I), R
7Alkyl for C1-C4.
2. preparation method according to claim 1, wherein, the pH value of described alkaline condition is 8-12, the pH value of described acidic conditions is 1-6.
3. preparation method according to claim 1, wherein, the compound of described structural formula (II) carries out translocation reaction by the compound shown in the structural formula (III) and makes in the presence of catalyzer and organic solvent, described catalyzer is at least a in 4-Dimethylamino pyridine, acetone cyanohydrin, sodium cyanide, potassium cyanide, cuprous cyanide, zinc chloride and the aluminum chloride;
Wherein, R
1-R
7Definition and claim 1 in identical.
4. preparation method according to claim 3, wherein, the condition of described translocation reaction comprises: the mol ratio of the compound of described catalyzer and described structural formula (III) is 0.02-0.5: 1, temperature of reaction is 0-110 ℃, the reaction times is 3-5 hour.
5. preparation method according to claim 4, wherein, the condition of described translocation reaction comprises: the mol ratio of the compound of described catalyzer and described structural formula (III) is 0.05-0.2: 1, temperature of reaction is 15-55 ℃, the reaction times is 3.5-4.5 hour.
6. according to any described preparation method among the claim 3-5, wherein, at least a as in benzene,toluene,xylene, ethylene dichloride, tetracol phenixin, trichloromethane and the methylene dichloride of the organic solvent that uses in the described translocation reaction.
7. preparation method according to claim 3, wherein, the compound of described structural formula (III) carries out condensation reaction by compound shown in the structural formula (IV) and the compound shown in the structure formula V and makes in the presence of acid binding agent and organic solvent,
Wherein, R
1-R
7Definition and claim 1 in identical, X is a halogen.
8. preparation method according to claim 7, wherein, described condensation reaction condition comprises: the mol ratio of the compound of the compound of described structure formula V and structural formula (IV) is 0.9-1.2: 1; The mol ratio of the compound of the consumption of described acid binding agent and described structural formula (IV) is 1-5: 1; Temperature of reaction is 0-110 ℃, and the reaction times is 0.5-2 hour.
9. preparation method according to claim 8, wherein, described condensation reaction condition comprises: the mol ratio of the compound of the compound of described structure formula V and structural formula (IV) is 1-1.1: 1; The mol ratio of the compound of the consumption of described acid binding agent and described structural formula (IV) is 1-2: 1; Temperature of reaction is 10-60 ℃, and the reaction times is 1-1.5 hour.
10. according to any described preparation method among the claim 7-9, wherein, described acid binding agent is at least a in Trimethylamine 99, triethylamine, tripropyl amine, pyridine, yellow soda ash and the salt of wormwood; At least a as in benzene,toluene,xylene, ethylene dichloride, tetracol phenixin, trichloromethane and the methylene dichloride of the organic solvent that uses in the described condensation reaction.
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| CN106565560A (en) * | 2016-11-11 | 2017-04-19 | 湖北广富林生物制剂有限公司 | Synthesis process of mesotrione |
| CN110078647B (en) * | 2019-05-15 | 2021-04-13 | 北京颖泰嘉和生物科技股份有限公司 | Post-treatment method of mesotrione reaction product |
| CN113845449B (en) * | 2020-06-28 | 2023-07-25 | 沈阳中化农药化工研发有限公司 | Method for preparing mesotrione herbicide |
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| CN85109771A (en) * | 1984-12-20 | 1987-07-29 | 斯托弗化学公司 | The preparation and the application of 2-(2-oil of mirbane formyl)-hydroresorcinol compounds |
| WO2004052849A1 (en) * | 2002-12-12 | 2004-06-24 | Nippon Soda Co.,Ltd. | Benzoyl derivative having sulfoximine group and herbicide |
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| CN85109771A (en) * | 1984-12-20 | 1987-07-29 | 斯托弗化学公司 | The preparation and the application of 2-(2-oil of mirbane formyl)-hydroresorcinol compounds |
| WO2004052849A1 (en) * | 2002-12-12 | 2004-06-24 | Nippon Soda Co.,Ltd. | Benzoyl derivative having sulfoximine group and herbicide |
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